The present invention generally relates to a device for detecting the presence of specific biological material in a sample, and more particularly to a laser compact disc system for detecting the presence of biological pathogens and/or analyte molecules bound to target receptors on the disc by sensing changes in the far-field diffracted intensity of the light along the optic axis of the laser caused by the pathogens and/or analytes.
In many chemical, biological, medical, and diagnostic applications, it is desirable to detect the presence of specific molecular structures in a sample. Many molecular structures such as cells, viruses, bacteria, toxins, peptides, DNA fragments, and antibodies are recognized by particular receptors. Biochemical technologies including gene chips, immulogical chips, and DNA arrays for detecting gene expression patterns in cancer cells, exploit the interaction between these molecular structures and the receptors as described in document numbers 8-11 of the list of documents provided at the end of this specification, all of which are hereby expressly incorporated herein by reference. These technologies generally employ a stationary chip prepared to include the desired receptors (those which interact with the molecular structure under test or analyte). Since the receptor areas can be quite small, chips may be produced which test for a plurality of analytes. Ideally, many thousand binding receptors are provided to provide a complete assay. When the receptors are exposed to a biological sample, only a few may bind a specific protein or pathogen. Ideally, these receptor sites are identified in as short a time as possible.
One such technology for screening for a plurality of molecular structures is the so-called immunlogical compact disk, which simply includes an antibody microarray. [See documents 16-18]. Conventional fluorescence detection is employed to sense the presence in the microarray of the molecular structures under test. This approach, however, is characterized by the known deficiencies of fluorescence detection, and fails to provide a capability for performing rapid repetitive scanning.
Other approaches to immunological assays employ traditional Mach-Zender interferometers that include waveguides and grating couplers. [See documents 19-23]. However, these approaches require high levels of surface integration, and do not provide high-density, and hence high-throughput, multi-analyte capabilities.
The present invention provides a biological, optical compact disk (xe2x80x9cbio-optical CDxe2x80x9d) system including a CD player for scanning biological CDs, which permit use of an interferometric detection technique to sense the presence of particular analyte in a biological sample. In one embodiment, binding receptors are deposited in the metallized pits of the CD (or grooves, depending upon the structure of the CD) using direct mechanical stamping or soft lithography. [See document 1-7]. In another embodiment, mesas or ridges are used instead of pits. Since inkpad stamps can be small (on the order of a square millimeter), the chemistry of successive areas of only a square millimeter of the CD may be modified to bind different analyte. A CD may include ten thousand different xe2x80x9csquaresxe2x80x9d of different chemistry, each including 100,000 pits prepared to bind different analyte. Accordingly, a single CD could be used to screen for 10,000 proteins in blood to provide an unambiguous flood screening.
Once a CD is prepared and exposed to a biological sample, it is scanned by the laser head of a modified CD player which detects the optical signatures (such as changes in refraction, surface shape, or absorption) of the biological structures bound to the receptors within the pits. In general, each pit is used as a wavefront-splitting interferometer wherein the presence of a biological structure in the pit affects the characteristics of the light reflected from the pit, thereby exploiting the high sensitivity associated with interferometeric detection. For large analytes such as cells, viruses and bacteria, the interferemeter of each pit is operated in a balanced condition wherein the pit depth is xcex4. For small analytes such as low-molecular weight antigens where very high sensitivity is desirable, each pit interferometer is operated in a phase-quadrature condition wherein the pit depth is xcex/8. The sensitivity can be increased significantly by incorporating a homodyne detection scheme, using a sampling rate of 1 Mbps with a resolution bandwidth of less than 1 kHz. Since pit-to-pit scan times are less than a microsecond, one million target receptors may be assessed in one second.
These and other features of the invention will become more apparent and the invention will be better understood upon review of the following specifications and accompanying drawings.